The objective of this proposal is to develop a lithium ion-selective electrode, primarily for application to the clinical determination of lithium in patients undergoing therapy for manic depression. The lithium electrodes currently available are not sufficiently selective for lithium relative to sodium. The selectivity of these electrodes is determined by the metal affinities of organic molecules that function as ion carriers in polymer membranes. Improved lithium ionophores would enable molecules that function as ion carriers in polymer membranes. Improved lithium ionophores would enable automated analysis of whole blood with minimal handling of blood products by the operator. Similar electrodes for calcium, sodium and potassium are already in use in the clinical analyzer market. The major goal of the proposed project is to improve the lithium selectivity of the most promising family of lithium ionophores by covalent attachment of the ionophores to flexible ethylene oxide and siloxane polymers. This covalent attachment of the ionophores to a polymer backbone should help reduce aggregation and improve the lithium/sodium selectivity by preventing the formation of 2:1 complexes of the ionophore and sodium.